AACR-FCPR: Ovarian Cancer More Aggressive With Age

Action Points

Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Explain that older age is associated with an increased risk of aggressive and rapidly fatal ovarian cancer.

Note that modifiable risk factors for ovarian cancer may have important implications for diagnosis and management of ovarian cancer in older women.

BOSTON -- Older women who developed ovarian cancer had a significantly greater likelihood of rapidly progressive, fatal disease, data from two large cohort studies showed.

The hazard for fatal ovarian cancer increased by 5% for each one-year increase in age at diagnosis. Postmenopausal status increased the hazard by 31% compared with women who were premenopausal at diagnosis in a cohort of women living in Massachusetts and New Hampshire.

Data from a larger, geographically diverse population showed a similar effect of age on ovarian cancer aggressiveness, as older age was associated with a 6% greater risk of rapidly fatal disease as compared with less aggressive cancer.

Both studies showed a protective effect of oral contraceptives on the risk of aggressive ovarian cancer, and one suggested that combined hormone replacement therapy is more closely associated with less aggressive disease, as reported here at the American Association for Cancer Research Frontiers in Cancer Prevention Research conference.

"The results in these two different groups of women are quite consistent and support an association between older age and more aggressive ovarian cancer," said Melissa A. Merritt, ScD, of the Harvard School of Public Health in Boston.

Studies that identify risk factors for ovarian cancer, particularly modifiable factors, have important implications for diagnosis and management of ovarian cancer in older women, added Elizabeth M. Poole, ScD, also of Harvard School of Public Health.

"Older women are a growing segment of the population, and we really have nothing to offer them to reduce the risk of ovarian cancer," Poole told MedPage Today. "These studies suggest some things that might be helpful, but the results are very preliminary."

Studies have shown that reproductive and hormonal factors contribute to a woman's risk of ovarian cancer. Whether those factors also influence ovarian cancer mortality was unclear.

Merritt presented findings from an analysis of participants in the New England-Based Case-Control Studies (NECC). The analysis included 1,642 women who had a history of ovarian cancer and a control group of 2,100 women with no history of ovarian cancer, enrolled in NECC from 1992 to 2008.

At enrollment, each participant was interviewed in detail about known and suspected risk factors for ovarian cancer, including hormone use, parity, lifestyle habits, and anthropomorphic characteristics. The primary objective was to determine whether a risk factor had a different association with fatal (death within three years of diagnosis) versus nonfatal ovarian cancer.

Merritt reported that 360 (22%) women with ovarian cancer died within three years. Multivariate analysis showed that increasing age was associated with an odds ratio of 1.05 for fatal versus nonfatal ovarian cancer (P<0.0001, for each one year of age). Postmenopausal status at diagnosis was associated with an odds ratio of 1.31 for fatal ovarian cancer, as compared with pre- or dubious menopausal status (P<0.0001).

Use of oral contraceptives was consistently associated with a lower risk of fatal ovarian cancer across all durations of use (P=0.01).

Factors that did not differ with respect to their influence on fatal versus nonfatal ovarian cancer included tubal ligation, total number of ovulatory years, body mass index (BMI), and family history of breast or ovarian cancer.

Poole presented data from an analysis that encompassed 30 years of follow up in the Nurses' Health Study. The primary objective was to examine risk-factor associations with rapidly fatal versus less aggressive ovarian cancer.

Death within three years of diagnosis was used to define aggressive, rapidly fatal ovarian cancer. Investigators identified 349 women who had rapidly fatal ovarian cancer and 404 who had less aggressive disease.

Combined estrogen-progestin hormone therapy was associated with an increased hazard for less aggressive disease (HR 1.52) but not rapidly fatal ovarian cancer (HR 0.91, P=0.02 for heterogeneity). Use of oral contraceptives reduced the risk of rapidly fatal ovarian cancer (HR 0.92 per each one year of use) but not less aggressive cancer (HR 1.00, P=0.003 for heterogeneity).

Parity (any children) reduced the risk of aggressive cancer (HR 0.58) but the number of children did not. Conversely, any parity did not reduce the risk of less aggressive disease, but an increasing number of children did (HR 0.90, P=0.02 for heterogeneity).

Duration of breastfeeding was associated with a reduced risk of rapidly fatal ovarian cancer (P=0.03), whereas height, BMI, age at menarche, age at menopausal, and tubal ligation did not differ in its impact on aggressive versus less aggressive cancer.

"We need to continue looking for ways to reduce the risk of rapidly fatal ovarian cancer in older women," Poole said. "Older women stop using oral contraceptives, and the protective effect wears off over time. Hormonal therapy did not affect the risk of aggressive, rapidly fatal disease."

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